RESUMO
As a direct result of the rapid technical progress which has been realized regarding hardware and software, cardiovascular magnetic resonance imaging (CMR) is increasingly established as an important method in the diagnosis of cardiovascular disease. Numerous clinical and experimental studies have demonstrated the equality or even superiority of CMR compared to other imaging modalities such as nuclear medicine or transthoracic echocardiography. Particular strengths of CMR are the ability to overcome anatomical limitations (such as poor acoustic window), a multimodality approach to comprehensively answer various aspects of cardiac disease, and the absence of ionizing radiation during the exam. Main clinical applications of CMR include assessment of ventricular function, myocardial viability, myocardial perfusion, valvular disease, differential diagnosis of inflammatory heart disease and cardiomyopathies, congenital heart disease and structural abnormalities. In the assessment of coronary artery disease (CAD) by CMR, analysis of global and regional myocardial function is enhanced by examination of myocardial viability and perfusion. This non-invasive diagnostic ''triad'' confers CMR a unique methodological strength for a comprehensive evaluation of CAD within one single exam session. In particular, late gadolinium enhancement scar imaging by CMR is currently the most accurate non-invasive method to examine myocardial viability. In several studies on the prognostic value of CMR in CAD assessment, normal adenosine-stress CMR was highly predictive for a good prognosis, thus able to identify patients in whom invasive coronary angiography can be deferred safely. Regarding myocarditis, CMR is evolving as the most accurate imaging technique. Challenges for future development of the role of CMR in clinical routine will most likely not only include technical improvement, but also a larger CMR scanner availability, optimized cost-efficiency, increased awareness and competence to be achieved by an extended education and training in CMR.
Assuntos
Cardiomiopatias/diagnóstico , Doenças das Valvas Cardíacas/diagnóstico , Imageamento por Ressonância Magnética , Isquemia Miocárdica/diagnóstico , Miocardite/diagnóstico , Cardiomiopatias/fisiopatologia , Meios de Contraste , Doença da Artéria Coronariana/diagnóstico , Diagnóstico Diferencial , Medicina Baseada em Evidências , Gadolínio , Cardiopatias Congênitas/diagnóstico , Testes de Função Cardíaca , Doenças das Valvas Cardíacas/fisiopatologia , Humanos , Angiografia por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/economia , Isquemia Miocárdica/fisiopatologia , Miocardite/fisiopatologia , Medição de Risco , Sensibilidade e Especificidade , Função Ventricular EsquerdaRESUMO
BACKGROUND: Studies in HIV-1 infected long-term non-progressors could demonstrate a strong HIV-1-specific CTL response, but it is difficult to prove that this strong CTL response actually is the cause of the efficient control of HIV-1 and not the consequence of low HIV-1 replication in these patients. OBJECTIVE: Studies of HIV-1-specific immunity and viral replication in patients undergoing immunosuppressive therapy provide important opportunities to understand the role of HIV-1-specific T-cells. RESULTS: In this report we describe an HLA B27 positive patient with normal CD4 counts and a low viral load of 200 copies/ml without antiretroviral therapy who exhibited a very strong HIV-1-specific CTL response. He had to be treated with steroids, NSAIDS and hydroxchloroquine because of a severe inflammatory reactive arthritis triggered by an acute Chlamydia trachomatis infection. Analysis of HIV-1 specific T-cells by gamma-IFN-ELISPOT revealed a high frequency of HIV-1 gag-specific CTL both in blood and synovial fluid, whereas gag-specific CD4-cells could be detected only in the peripheral blood. Further analysis revealed that the gag-specific T-cells were predominantly targeting the HLA B27-restricted CTL epitope KRWIILGLNK (KK10). Immunosuppressive therapy by prednisone was associated with a moderate increase of HIV-1 viremia and a decrease both in the number and in the gamma-IFN production of KK10-specific CTL indicating that inhibition of CTL function contributed to the increase of viral load. CONCLUSIONS: This study is suggesting that HIV-1 specific CTL play an important role in the control of HIV-1, at least in this patient. Inhibition of CTL function by immunosuppressive therapy with prednisone may enhance viral replication. In addition, we could demonstrate for the first time the migration of HIV-1 specific T-cells into the synovial fluid.
Assuntos
Artrite Reativa/complicações , Infecções por Chlamydia/complicações , Infecções por HIV/complicações , Imunossupressores/efeitos adversos , Linfócitos T Citotóxicos/imunologia , Adulto , Artrite Reativa/tratamento farmacológico , Infecções por Chlamydia/tratamento farmacológico , Chlamydia trachomatis , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/imunologia , Humanos , Masculino , Carga ViralRESUMO
The aetiological spectrum of thoracic aortic aneurysms is extensive. Infectious aneurysms (formerly mycotic aneurysms) constitute only a small percentage of all thoracic aortic aneurysms, they are usually small and often develop as complications of bacterial endocarditis. We report the case of a 39-year-old insulin-dependent diabetic, who developed a leaking aneurysm of the thoracic aorta as a late complication of a knee empyema with subsequent metastatic mediastinitis. Clinical, radiological, biochemical and microbiological data are correlated with histopathological findings. The development of this unusual thoracic aortic aneurysm is shown from impending rupture to successful vascular graft implantation.
Assuntos
Aneurisma da Aorta Torácica/patologia , Aneurisma da Aorta Torácica/cirurgia , Neoplasias do Mediastino/patologia , Neoplasias do Mediastino/secundário , Adulto , Aneurisma da Aorta Torácica/diagnóstico por imagem , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/patologia , Empiema/complicações , Humanos , Artropatias/complicações , Artropatias/patologia , Articulação do Joelho , Masculino , Neoplasias do Mediastino/diagnóstico por imagem , Neoplasias do Mediastino/cirurgia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Heterotopic ossification as newly formed bone in extraosseous tissue is an uncommon finding in atherosclerotic lesions. The exact mechanisms and development of bone formation in regard to late stage calcified atherosclerosis still remains under debate. METHODS: We studied 400 autopsy carotid probes and 306 samples of atherosclerotic carotid endatherectomy. Radiographic analysis and classification of calcification was performed followed by light microscopy. In probes with detected ossifications further analysis using immunohistochemistry, scanning electron microscopy (SEM) and energy dispersive x-ray micro-analysis (EDX) including calcium mapping was performed. RESULTS: Ossification in atherosclerotic carotid arteries was a finding in only a minority of samples (5%) and occurred at sites of large calcific deposits. Histomorphology of bone formation equaled skeletal bone showing osteoblastic cells, osteocytes included in osteoid matrix, bone marrow and osteolytic giant multinucleated cells. Closely related to newly formed bone zones of neovascularization were found. Development of ossification seemed to occur in five stages (lipidous plaque, fibrous cellular plaque, fibrous acellular plaque, calcified plaque and osteogenesis). The environment of sites of ossification was characterized by a varying texture of extracellular fibrous matrix, foam cells, smooth muscle cells, fibroblasts and calcified deposits. CONCLUSIONS: Heterotopic ossifications of atherosclerotic plaques seem to be a specific differentiation of fibrous plaques. Components of atherosclerotic lesions like vascular wall cells, neovessels and matrix structures seem to be involved in the process of transformation to mature bone tissue.
Assuntos
Arteriosclerose/patologia , Calcinose/patologia , Estenose das Carótidas/patologia , Ossificação Heterotópica/patologia , Artérias Carótidas/patologia , Técnicas de Cultura , Humanos , Microscopia Eletrônica de VarreduraRESUMO
OBJECTIVE: The reverse transcriptase (RT) M184V mutation within the HLA-A2-restricted HIV-1 cytotoxic T lymphocyte (CTL) epitope VL9 (VIYQYMDDL; RT 179-187) not only induces drug escape against lamivudine but also abolished recognition by a CTL clone derived from a long-term non-progressor. To test whether the variant VL9 epitope containing the M184V mutation represents a new CTL epitope, we studied recognition of this epitope in a cohort of HLA-A2-positive HIV-1-infected patients. METHODS: Peripheral blood mononuclear cells isolated from 28 HIV-1-infected patients were stimulated with the peptide VIYQYVDDL, containing the M1 84V mutation. Outgrowing cell lines were tested for specific recognition in a standard chromium-release assay. RESULTS: In one subject, a CTL line could be isolated recognizing the peptide VIYQYVDDL in conjunction with HLA-A2. The CTL clone also recognized the M1841 mutation, but it failed to recognize the wild-type epitope VIYQYMDDL. CONCLUSION: CTL can specifically recognize lamivudine-resistant HIV-1 variants. Therefore, the cellular immune response could have an important influence on the control of drug-resistant virus. Furthermore, this demonstrates that the immune system can generate new CTL specificities even in patients with advanced disease, as the M184V HIV variants emerges only after drug treatment. Specific immunotherapy against this epitope might be helpful in delaying or preventing lamivudine resistance.
Assuntos
HIV-1/efeitos dos fármacos , HIV-1/imunologia , Lamivudina/farmacologia , Inibidores da Transcriptase Reversa/farmacologia , Linfócitos T Citotóxicos/imunologia , Adulto , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Linhagem Celular , Citotoxicidade Imunológica , Resistência Microbiana a Medicamentos , Quimioterapia Combinada , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Inibidores da Protease de HIV/uso terapêutico , Transcriptase Reversa do HIV/genética , HIV-1/genética , Antígeno HLA-A2/imunologia , Humanos , Ativação Linfocitária , Masculino , Mutação , Inibidores da Transcriptase Reversa/uso terapêuticoRESUMO
To study whether an expansion of HIV-1-specific CTL is contributing to the skewed TCR repertoire in HIV-1-infection, we characterized the TCR usage of CTL clones specific for a conserved epitope in HIV-1 reverse transcriptase (RT/476-484). CTL clones from three HIV-1-infected patients displayed highly similar TCR usage and used the identical Vbeta6.1 and Valpha2.5 gene segments. CTL clones from two patients showed a very high degree of similarity within the TCR complementarity-determining region-3 (CDR-3). In accordance with the similar molecular structure, all three CTL clones also exhibited a similar functional activity with regard to recognition of variant peptides and cytokine secretion pattern. In one subject clonal expansion of a single CTL specificity could be shown over a 10-mo period. TCR spectratyping of PBMC from two patients revealed a marked expansion of CDR-3 segments of a certain length within the Vbeta6-family. Sequence analysis of these CDR-3 yielded sequences identical to the RT/476-484-specific CTL previously isolated from the same patients. This analysis demonstrates that clonal expansion of HIV-1-specific CTL is contributing to the skewed TCR repertoire in HIV-1-infected patients.
Assuntos
Epitopos de Linfócito T/imunologia , Infecções por HIV/imunologia , Transcriptase Reversa do HIV/imunologia , Ativação Linfocitária/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/biossíntese , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismo , Sequência de Aminoácidos , Sequência de Bases , Separação Celular , Células Clonais , Citocinas/biossíntese , Citotoxicidade Imunológica , Rearranjo Gênico da Cadeia alfa dos Receptores de Antígenos dos Linfócitos T , Rearranjo Gênico da Cadeia beta dos Receptores de Antígenos dos Linfócitos T , Variação Genética/genética , Variação Genética/imunologia , Infecções por HIV/metabolismo , Humanos , Masculino , Dados de Sequência Molecular , Oligopeptídeos/genética , Oligopeptídeos/imunologia , Oligopeptídeos/metabolismo , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Proteínas Virais/genética , Proteínas Virais/imunologia , Proteínas Virais/metabolismoRESUMO
It has been hypothesized that sequence variation within CTL epitopes leading to immune escape plays a role in the progression of HIV-1 infection. Only very limited data exist that address the influence of biologic characteristics of CTL epitopes on the emergence of immune escape variants and the efficiency of suppression HIV-1 by CTL. In this report, we studied the effects of HIV-1 CTL epitope sequence variation on HIV-1 replication. The highly conserved HLA-B14-restricted CTL epitope DRFYKTLRAE in HIV-1 p24 was examined, which had been defined as the immunodominant CTL epitope in a long-term nonprogressing individual. We generated a set of viral mutants on an HX10 background differing by a single conservative or nonconservative amino acid substitution at each of the P1 to P9 amino acid residues of the epitope. All of the nonconservative amino acid substitutions abolished viral infectivity and only 5 of 10 conservative changes yielded replication-competent virus. Recognition of these epitope sequence variants by CTL was tested using synthetic peptides. All mutations that abrogated CTL recognition strongly impaired viral replication, and all replication-competent viral variants were recognized by CTL, although some variants with a lower efficiency. Our data indicate that this CTL epitope is located within a viral sequence essential for viral replication. Targeting CTL epitopes within functionally important regions of the HIV-1 genome could limit the chance of immune evasion.
Assuntos
Sequência Conservada/imunologia , Epitopos de Linfócito T/química , Epitopos de Linfócito T/fisiologia , Proteína do Núcleo p24 do HIV/imunologia , HIV-1/imunologia , Linfócitos T Citotóxicos/imunologia , Replicação Viral/imunologia , Animais , Variação Antigênica/genética , Células COS , Linhagem Celular Transformada , Progressão da Doença , Epitopos de Linfócito T/genética , Proteína do Núcleo p24 do HIV/química , Proteína do Núcleo p24 do HIV/genética , Proteína do Núcleo p24 do HIV/fisiologia , HIV-1/genética , Humanos , Tolerância Imunológica/genética , Masculino , Mutagênese Sítio-Dirigida , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/imunologia , Provírus/genética , Linfócitos T Citotóxicos/metabolismo , Transfecção , Replicação Viral/genéticaRESUMO
HIV-1 infection has been shown to elicit strong CTL responses in some infected persons, but few data are available regarding the relationship between targeted epitopes and in vivo viral quasispecies. In this study, we examined the CTL response in a person infected for 15 yr with a CD4 count persistently >500 cells/microl. The dominant in vivo activated CTL response was directed against two overlapping Gag CTL epitopes in an area of p17 known to be essential for viral replication. The 9-mer SLYNTVATL (amino acids 77-85) was recognized in conjunction with HLA-A2, whereas the overlapping 8-mer TLYCVHQR (amino acids 83-91) was recognized by HLA-A11-restricted CTL. Analysis of in vivo virus sequences both in PBMC and plasma revealed the existence of sequence variation in this region, which did not affect viral replication in vitro, but decreased recognition by the A11-restricted CTL response, with maintenance of the A2-restricted response. These results indicate that an essential region of the p17 protein can be simultaneously targeted by CTL through two different HLA molecules, and that immune escape from CTL recognition can occur without impairing viral replication. In addition, they demonstrate that Ag processing can allow for presentation of overlapping epitopes in the same infected cell, which can be affected quite differently by sequence variation.
Assuntos
Apresentação de Antígeno , Variação Antigênica , Epitopos/imunologia , Produtos do Gene gag/imunologia , Antígenos HIV/imunologia , Sobreviventes de Longo Prazo ao HIV , HIV-1/imunologia , Antígenos HLA-A/imunologia , Antígeno HLA-A2/imunologia , Linfócitos T Citotóxicos/imunologia , Proteínas Virais , Sequência de Aminoácidos , Animais , Contagem de Linfócito CD4 , Células COS , Progressão da Doença , Produtos do Gene gag/genética , Antígenos HIV/genética , HIV-1/genética , HIV-1/fisiologia , Antígeno HLA-A11 , Humanos , Masculino , Dados de Sequência Molecular , Fragmentos de Peptídeos/imunologia , Provírus/genética , Transfecção , Carga Viral , Replicação Viral , Produtos do Gene gag do Vírus da Imunodeficiência HumanaRESUMO
A prominent feature of HIV infection is a progressive anergy of T cells and an increase of activation-dependent T-cell death. CD80 (B7.1), the ligand of CD28, is an important co-stimulatory molecule on antigen-presenting cells that delivers an essential second signal for T-cell activation. To test whether immunologic dysfunction in HIV disease involves CD80, we studied CD80 expression on circulating monocytes in heparinized whole blood of 33 HIV-infected patients and 13 controls. Most monocytes in patients and controls expressed significant amounts of CD80. There was no statistical difference of mean fluorescence intensity (MFI) of CD80 expression when all HIV-infected patients were compared with healthy controls. However, asymptomatic patients in clinical Centers for Disease Control and Prevention (CDC) stage A showed a significantly stronger CD80 expression than did healthy controls. Additionally, patients receiving antiretroviral therapy exhibited significantly higher CD80 expression than did patients not receiving therapy and healthy controls. We did not find a correlation with the presence of HIV p24 antigenemia and counts of CD4+ and CD8+ T cells. Although we studied CD80 expression only on circulating monocytes and not in HIV-infected monocytes or in activated macrophages, our data do not support a role for a general impairment of CD80 expression in induction of anergy in HIV disease.
Assuntos
Antígeno B7-1/análise , Infecções por HIV/imunologia , Monócitos/química , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Zidovudina/uso terapêuticoRESUMO
Some individuals in well-defined cohorts have now been infected with HIV-1 for well over a decade and yet remain clinically asymptomatic with normal CD4 counts. To determine immunologic and virologic parameters in these individuals, we examined 10 persons from the San Francisco City Clinic with firmly documented infection of 11-15 years duration who had maintained stable CD4 counts above 500 cells/microliters. Our results indicate that long-term nonprogressors are a heterogeneous group with respect to viral load and HIV-1-specific immune responses, and that progression can occur even after 15 years of stable infection. However, in a subset of persons with the lowest viral loads and persistent nonprogressive infection, we detected strong CTL responses, whereas neutralizing antibody studies revealed weak to undetectable titers against a panel of 10 primary isolates. This study demonstrates that a vigorous in vivo activated HIV-1-specific CTL response can be part of the host immune response in stable nonprogressive HIV-1 infection, and that circulating activated CTL can be detected in the setting of an extremely low viral load. These results also indicate that long-term nonprogressing HIV-1 infection does not require the presence of broadly cross-reactive neutralizing antibodies.
Assuntos
Anticorpos Anti-HIV/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Linfócitos T Citotóxicos/imunologia , Linhagem Celular Transformada , Progressão da Doença , Infecções por HIV/virologia , HIV-1/crescimento & desenvolvimento , Humanos , Masculino , Testes de Neutralização , SobreviventesRESUMO
Numerous virus-specific, class I-restricted cytotoxic T lymphocyte (CTL) epitopes have been identified, yet little information is available regarding the specificity of the CTL response in persons of the same human histocompatibility leukocyte antigen (HLA) type. In this study, the human immunodeficiency virus (HIV) 1 envelope-specific CTL response was evaluated in five HLA-B14-positive persons. CTL responses specific for a previously described nine-amino acid epitope in gp41 (aa 584-592, ERYLKDQQL) could be identified in all subjects, and CTL clones specific for this epitope could be isolated from four persons. Despite heterogeneous T cell receptor usage, the fine specificity of the clones was similar, as defined by recognition of alanine-substituted peptides as well as peptides representing natural HIV-1 sequence variants. Correlation with in vivo virus sequences revealed that the dominant species in two of the subjects represented poorly recognized variants, with a K-->Q substitution at amino acid 588, whereas no variants were observed in the other two subjects. Although clonal type-specific responses to these dominant variants could be identified, the magnitude of these responses remained small, and the dominant CTL response was directed at the minor in vivo variant. These studies indicate that despite similar epitope-specific immunologic pressure in persons of the same HLA type, the in vivo quasispecies may differ, and that the major in vivo immune response to a given CTL epitope can be directed at a minor variant.
Assuntos
Proteína gp41 do Envelope de HIV/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Antígenos HLA-B/imunologia , Fragmentos de Peptídeos/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Linfócitos T Citotóxicos/imunologia , Sequência de Aminoácidos , Antígenos Virais/genética , Antígenos Virais/imunologia , Sequência de Bases , Células Clonais , Variação Genética , Proteína gp41 do Envelope de HIV/genética , HIV-1/genética , Antígeno HLA-B14 , Teste de Histocompatibilidade , Humanos , Epitopos Imunodominantes/genética , Epitopos Imunodominantes/imunologia , Masculino , Dados de Sequência Molecular , Fragmentos de Peptídeos/genética , Análise de Sequência de DNA , Homologia de Sequência , Especificidade da Espécie , Linfócitos T Citotóxicos/citologiaRESUMO
Although vigorous activated and memory CTL have been associated with HIV-1 infection, data are lacking regarding the breadth of epitopes recognized in a given individual and the relationship to the viral quasispecies present in vivo. In this study we performed a detailed analysis of the HIV-1-specific CTL response in a seropositive person with documented HIV-1 infection of 15 yr duration, stable CD4 counts above 500 cells/ml, and viral load persistently below 500 molecules of RNA/ml of plasma. Epitope mapping studies revealed the presence of HLA class I-restricted CTL responses to six different epitopes in p17, p24, RT, Env, and Nef, which conferred broadly cross-reactive recognition of reported HIV-1 variants. Sequence analysis of autologous viruses revealed the absence of immune escape variants within five of the six epitopes. Despite consistently low viral RNA levels in plasma and viral DNA levels in PBMC, in vivo-activated circulating CTL were detected against three of the epitopes. Five of the six epitopes, including the three dominant epitopes, have been detected in persons with progressive disease, suggesting that nonprogressors may not target unique epitopes. This study demonstrates that HIV-1-specific CTL can be highly activated and broadly directed in the setting of an extremely low viral load, and that neither high viral load nor antigenic diversity is required for the generation of a multispecific CTL response. Although the detection of strong CTL responses, low viral load, and lack of immune escape are consistent with the hypothesis that CTL may contribute to lack of disease progression in this individual, the contribution of these responses to maintenance of the asymptomatic state remains to be determined.
Assuntos
Infecções por HIV/imunologia , HIV-1 , Linfócitos T Citotóxicos/imunologia , Sequência de Aminoácidos , Sequência de Bases , Contagem de Linfócito CD4 , Reações Cruzadas , Citotoxicidade Imunológica , Primers do DNA/genética , DNA Viral/genética , Mapeamento de Epitopos , Variação Genética , Antígenos HIV/genética , Infecções por HIV/virologia , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Memória Imunológica , Técnicas In Vitro , Leucócitos Mononucleares/imunologia , Ativação Linfocitária , Dados de Sequência Molecular , Fatores de Tempo , Viremia/imunologiaRESUMO
The human immunodeficiency virus (HIV) type 1 reverse transcriptase (RT) is an important target for therapeutic intervention and for HIV-1-specific cytotoxic T lymphocytes (CTL). An HLA-A2-restricted CTL epitope containing the sequence YMDD, which is highly conserved among human and animal retroviruses and essential for function of the RNA-dependent DNA polymerase, is identified. The drug resistance mutation at RT amino acid 184 (M184V), associated with (-)-2'-deoxy-3'-thiacytidine (lamivudine), (-)-2'-deoxy-5-fluoro-3'-thiacytidine (FTC), and dideoxyinosine resistance, is located within this epitope and abolishes recognition by an established CTL response. This study demonstrates that the CTL response may target functionally relevant regions of the RT protein and suggests drug therapy may select for viral variants with altered susceptibility to established cellular immune responses.
Assuntos
Infecções por HIV/imunologia , HIV-1/imunologia , Antígeno HLA-A2/imunologia , DNA Polimerase Dirigida por RNA/imunologia , Linfócitos T Citotóxicos/imunologia , Sequência de Aminoácidos , Antivirais/farmacologia , Sequência de Bases , Sequência Conservada , Primers do DNA/química , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Didanosina/farmacologia , Resistência Microbiana a Medicamentos , Epitopos/imunologia , Infecções por HIV/fisiopatologia , Transcriptase Reversa do HIV , HIV-1/enzimologia , Humanos , Lamivudina , Dados de Sequência Molecular , Oligopeptídeos/química , Oligopeptídeos/imunologia , Reação em Cadeia da Polimerase , DNA Polimerase Dirigida por RNA/química , DNA Polimerase Dirigida por RNA/efeitos dos fármacos , Zalcitabina/análogos & derivados , Zalcitabina/farmacologiaAssuntos
Soropositividade para HIV/imunologia , HIV-1/imunologia , Linfócitos T Citotóxicos/imunologia , Sequência de Aminoácidos , Epitopos/genética , Antígenos HIV/genética , Antígenos HIV/imunologia , Transcriptase Reversa do HIV , Humanos , Técnicas In Vitro , Dados de Sequência Molecular , DNA Polimerase Dirigida por RNA/genética , DNA Polimerase Dirigida por RNA/imunologia , Fatores de TempoRESUMO
CD8-positive cytotoxic T cells (CTLs) are activated by recognition of peptide bound to MHC class I molecules on target cells. This human leukocyte antigen-restricted process induces not only lysis of target cells but also secretion of lymphokines by the CTLs, including TNF-alpha, TNF-beta, and IFN-gamma. In this study we show that activation of HIV-1-specific CTL clones by their cognate peptide epitopes induces HIV-1 replication in the chronically HIV-1-infected T-cell line ACH-2. The HIV-1-inducing activity correlates with increased levels of TNF-alpha produced by these CTLs, and can be inhibited by anti-TNF-alpha antibodies, indicating that the effect is mediated by this cytokine. These studies suggest that activation of CTL in vivo could lead to enhanced viral replication. Although HIV-1-specific CTLs may serve as a host defense to inhibit virus replication, the induction of TNF-alpha production by these cells may facilitate viral replication in infected bystander cells, contributing to viral persistence and disease pathogenesis.